Migraine prevention and treatment

Abstract

The invention relates to a compound for use in a method of treatment or prevention of migraine and/or symptoms thereof. The compound is selected from beta-hydroxybutyric acid (βHB) or a pharmaceutically acceptable salt thereof, acetoacetate (AcAc) or a pharmaceutically acceptable salt thereof, a metabolic precursor of βHB or AcAc 1,3-butanedio and a compound comprising an acetoacetyl- or 3-hydroxybutyrate moiety. The invention further relates to a pharmaceutical composition comprising βHB, AcAc or a pharmaceutically acceptable salt thereof.

The invention claimed is: 
     
       1. A method of treatment or prevention of migraine and/or symptoms thereof in a patient in need thereof, said method comprising administering to the patient a compound selected from the group consisting of
 a. beta-hydroxybutyric acid (βHB) or a pharmaceutically acceptable salt thereof, 
 b. acetoacetate (AcAc) or a pharmaceutically acceptable salt thereof, 
 c. a metabolic precursor of βHB or AcAc selected from
 1,3-butanediol (CAS No. 107 88 0) and 
 triacetin (CAS No. 102-76-1), 
 or a pharmaceutically acceptable salt thereof, and 
 
 d. a compound having an acetoacetyl- or 3-hydroxybutyrate moiety, wherein said compound is
 (i) described by any one of: 
 “D beta-hydroxybutyrate-D-1,3-butanediol”, 
 “(3R)-hydroxybutyl-(3R)-hydroxybutyrate”, 
 “acetoacetyl-1,3-butanediol”, 
 “acetoacetyl-R-3-hydroxybutyrate,” and 
 “acetoacetylglycerol”, or 
 (ii) described by any one of the formulae: 
 
 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
       2. The method of treatment or prevention of migraine and/or symptoms according to claim, wherein said compound is selected from βHB, a metabolic precursor of βHB, a compound having a 3-hydroxybutyrate moiety, and a pharmaceutically acceptable salt thereof. 
     
     
       3. The method of treatment or prevention of migraine and/or symptoms thereof according to  claim 1 , wherein said compound is βHB, or a pharmaceutically acceptable salt thereof. 
     
     
       4. The method of treatment or prevention of migraine and/or symptoms thereof according to  claim 1 , wherein said compound is D-βHB, or a pharmaceutically acceptable salt thereof. 
     
     
       5. The method of treatment or prevention of migraine and/or symptoms thereof according to  claim 1 , wherein said pharmaceutically acceptable salt is selected from a potassium salt, a sodium salt, a calcium salt, a magnesium salt, an arginine salt, a lysine salt, a histidine salt, an ornithine salt, a creatine salt, an agmatine salt, a citrulline salt, a methyl glucamine salt and a carnitine salt, or a combination of said salts. 
     
     
       6. The method of treatment or prevention of migraine and/or symptoms thereof according to  claim 5 , wherein said combination of salts comprises a combination of a lysine salt and a calcium, potassium, magnesium and/or sodium salt. 
     
     
       7. The method of treatment or prevention of migraine and/or symptoms thereof according to  claim 1 , wherein said treatment or prevention includes decreasing migraine attack frequency; decreasing migraine attack severity; decreasing the severity of migraine symptoms; preventing disease progression; or preventing disease chronification. 
     
     
       8. The method of treatment or prevention of migraine and/or symptoms thereof according to  claim 1 , wherein said symptoms of migraine include at least two symptoms selected from the group consisting of: medium to strong predominantly unilateral headache; light; noise and/or smell sensitivity; nausea or sickness; facial pain; sore eyes; balance disturbance; word finding difficulties; sensory or motor disturbances; allodynia; at least one symptom known to accompany, precede or follow a migraine attack selected from fatigue, nausea, cognitive difficulties, tiredness, ravenous hunger or thirst, reduced libido, depression, mania, mood swings, and at least one change in brain structure and function. 
     
     
       9. The method of treatment or prevention of migraine and/or symptoms thereof according to  claim 1 , wherein said compound is to be administered before occurrence of one or more of the symptoms of a migraine attack according to  claim 8 . 
     
     
       10. The method of treatment or prevention of migraine and/or symptoms thereof according to  claim 1 , wherein the daily dose to be administered is 0.05 g/kg to 1 g/kg body weight. 
     
     
       11. The method of treatment or prevention of migraine and/or symptoms thereof according to  claim 10 , wherein said daily dose is divided into one to six doses. 
     
     
       12. The method of treatment or prevention of migraine and/or symptoms thereof according to  claim 10 , wherein said daily dose is to be administered over a time period of at least one month. 
     
     
       13. The method of treatment or prevention of migraine and/or symptoms thereof according to  claim 1 , wherein the administration of said pharmaceutical composition to a subject causes elevation of blood ketone body (KB) levels to 0.3 mM to 6 mM. 
     
     
       14. A method of treatment or prevention of migraine and/or symptoms thereof in a patient in need thereof comprising administering to the patient a pharmaceutical composition comprising the compound according to  claim 1 . 
     
     
       15. The method according to  claim 14 , wherein said pharmaceutical composition is a combination medicament further comprising an amino acid selected from the group consisting of leucine, lysine, isoleucine, tryptophan, tyrosine and phenylalanine. 
     
     
       16. The method according to  claim 14 , wherein the pharmaceutical composition comprises at least 25% (w/w) of the compound according to  claim 1 . 
     
     
       17. The method according to  claim 14 , wherein the pharmaceutical composition is formulated for oral administration. 
     
     
       18. The method according to  claim 17 , wherein the pharmaceutical composition is formulated as a powder for oral administration. 
     
     
       19. The method according to  claim 14 , wherein said pharmaceutical composition is a drink.